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Further Exploration of the Benzimidazole Scaffold as TRPC5 Inhibitors: Identification of 1‐Alkyl‐2‐(pyrrolidin‐1‐yl)‐1H‐benzo[d]imidazoles as Potent and Selective Inhibitors

The transient receptor potential cation channel 5 (TRPC5) plays an important role in numerous cellular processes. Due to this, it has gained considerable attention over the past few years as a potential therapeutic target. Recently, TRPC5 has been shown to be involved in the regulation of podocyte s...

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Autores principales: Sharma, Swagat, L. Pablo, Juan, Tolentino, Kirsten T., Gallegos, Wacey, Hinman, Jennifer, Beninato, Madison, Asche, MacKenzie, Greka, Anna, Hopkins, Corey R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308755/
https://www.ncbi.nlm.nih.gov/pubmed/35557491
http://dx.doi.org/10.1002/cmdc.202200151
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author Sharma, Swagat
L. Pablo, Juan
Tolentino, Kirsten T.
Gallegos, Wacey
Hinman, Jennifer
Beninato, Madison
Asche, MacKenzie
Greka, Anna
Hopkins, Corey R.
author_facet Sharma, Swagat
L. Pablo, Juan
Tolentino, Kirsten T.
Gallegos, Wacey
Hinman, Jennifer
Beninato, Madison
Asche, MacKenzie
Greka, Anna
Hopkins, Corey R.
author_sort Sharma, Swagat
collection PubMed
description The transient receptor potential cation channel 5 (TRPC5) plays an important role in numerous cellular processes. Due to this, it has gained considerable attention over the past few years as a potential therapeutic target. Recently, TRPC5 has been shown to be involved in the regulation of podocyte survival, indicating a potential treatment option for chronic kidney disease. In addition, a recent study has shown TRPC5 to be expressed in human sensory neurons and suggests that TRPC5 inhibition could be an effective treatment for spontaneous and tactile pain. To understand these processes more fully, potent and selective tool compounds are needed. Herein we report further exploration of the 2‐aminobenzimidazole scaffold as a potent TRPC5 inhibitor, culminating in the discovery of 16 f as a potent and selective TRPC5 inhibitor.
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spelling pubmed-93087552022-10-14 Further Exploration of the Benzimidazole Scaffold as TRPC5 Inhibitors: Identification of 1‐Alkyl‐2‐(pyrrolidin‐1‐yl)‐1H‐benzo[d]imidazoles as Potent and Selective Inhibitors Sharma, Swagat L. Pablo, Juan Tolentino, Kirsten T. Gallegos, Wacey Hinman, Jennifer Beninato, Madison Asche, MacKenzie Greka, Anna Hopkins, Corey R. ChemMedChem Research Articles The transient receptor potential cation channel 5 (TRPC5) plays an important role in numerous cellular processes. Due to this, it has gained considerable attention over the past few years as a potential therapeutic target. Recently, TRPC5 has been shown to be involved in the regulation of podocyte survival, indicating a potential treatment option for chronic kidney disease. In addition, a recent study has shown TRPC5 to be expressed in human sensory neurons and suggests that TRPC5 inhibition could be an effective treatment for spontaneous and tactile pain. To understand these processes more fully, potent and selective tool compounds are needed. Herein we report further exploration of the 2‐aminobenzimidazole scaffold as a potent TRPC5 inhibitor, culminating in the discovery of 16 f as a potent and selective TRPC5 inhibitor. John Wiley and Sons Inc. 2022-05-24 2022-07-19 /pmc/articles/PMC9308755/ /pubmed/35557491 http://dx.doi.org/10.1002/cmdc.202200151 Text en © 2022 The Authors. ChemMedChem published by Wiley-VCH GmbH https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Sharma, Swagat
L. Pablo, Juan
Tolentino, Kirsten T.
Gallegos, Wacey
Hinman, Jennifer
Beninato, Madison
Asche, MacKenzie
Greka, Anna
Hopkins, Corey R.
Further Exploration of the Benzimidazole Scaffold as TRPC5 Inhibitors: Identification of 1‐Alkyl‐2‐(pyrrolidin‐1‐yl)‐1H‐benzo[d]imidazoles as Potent and Selective Inhibitors
title Further Exploration of the Benzimidazole Scaffold as TRPC5 Inhibitors: Identification of 1‐Alkyl‐2‐(pyrrolidin‐1‐yl)‐1H‐benzo[d]imidazoles as Potent and Selective Inhibitors
title_full Further Exploration of the Benzimidazole Scaffold as TRPC5 Inhibitors: Identification of 1‐Alkyl‐2‐(pyrrolidin‐1‐yl)‐1H‐benzo[d]imidazoles as Potent and Selective Inhibitors
title_fullStr Further Exploration of the Benzimidazole Scaffold as TRPC5 Inhibitors: Identification of 1‐Alkyl‐2‐(pyrrolidin‐1‐yl)‐1H‐benzo[d]imidazoles as Potent and Selective Inhibitors
title_full_unstemmed Further Exploration of the Benzimidazole Scaffold as TRPC5 Inhibitors: Identification of 1‐Alkyl‐2‐(pyrrolidin‐1‐yl)‐1H‐benzo[d]imidazoles as Potent and Selective Inhibitors
title_short Further Exploration of the Benzimidazole Scaffold as TRPC5 Inhibitors: Identification of 1‐Alkyl‐2‐(pyrrolidin‐1‐yl)‐1H‐benzo[d]imidazoles as Potent and Selective Inhibitors
title_sort further exploration of the benzimidazole scaffold as trpc5 inhibitors: identification of 1‐alkyl‐2‐(pyrrolidin‐1‐yl)‐1h‐benzo[d]imidazoles as potent and selective inhibitors
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308755/
https://www.ncbi.nlm.nih.gov/pubmed/35557491
http://dx.doi.org/10.1002/cmdc.202200151
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